chr13-95074263-AC-GA

Variant names:

• chr13-95074263-AC-GA
• NM_005845.5:c.2867_2868delGTinsTC
• ABCC4 p.Cys956Phe

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005845.5(ABCC4):​c.2867_2868delGTinsTC​(p.Cys956Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78
• Publications: 0 publications found

Genes affected

ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ABCC4 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.2867_2868delGTinsTC	p.Cys956Phe	missense	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.2726_2727delGTinsTC	p.Cys909Phe	missense	N/A	NP_001288758.1	O15439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2867_2868delGTinsTC	p.Cys956Phe	missense	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000967420.1		c.2867_2868delGTinsTC	p.Cys956Phe	missense	N/A	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.2864_2865delGTinsTC	p.Cys955Phe	missense	N/A	ENSP00000637480.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-95726517;